Flashcards in CNS infections 1 Deck (75):
Most Common Agents of Congenital Infections
Herpes simplex virus [HSV]) -2 or -1
TORCH test: a series of tests for specific IgM in chord blood
(may be STORCH: syphilis)
one more: Lymphocytic choriomenigitis virus (LCMV)
HSV infections cause infection and morbidity in neonates:
Skin, Eye, Mouth
Disseminated disease with or without CNS disease
the leading cause (by far) of infection and morbidity in the neonate
40,000 neonates born in US/yr affected-->sequelae (hearing loss, vision loss, and cognitive impairment) in 1/5th of cases
nosocomial-acquired meningitis orgs
*half of all meningitis cases in US
Predisposing conditions for Nosocomial-acquired meningitis
recent neurological procedures.
presence of neurological devices.
altered immune status
??? is NOT a portal of entry for viral infection
Infection in the CNS is usually a secondary infection, occurring days, weeks, months, or years after the initial infection
bacterial meningitis vs. viral meningitis
used to be more but now we vaccinate against mumps?
many not def. ddx
bac meningitis neonate orgs
Streptococcus agalactiae, Escherichia coli
bac meningitis infant and young kiddo orgs
bac meningitis adolescents →Elderly orgs
>50-y-o: L. monocytogenes
The problem for the physician is to differentiate between bacterial pyogenic/purulent meningitis, which is a ?? and ?? viral meningitis
Symptoms of bacterial meningitis in the older child → adult include acute onset of:
*lethargy (altered mental status)
pressure on eyeball
the single most important predisposing factor for meningitis in the neonate
Low birth weight
Low birth weight (LBW;
What factors predispose the LBW, VLBW, and ELBW infant to infection?
Impaired innate and adaptive immune functions
if Require nosocomial techniques and devices to keep alive
Incidence of sepsis is much higher
Maternally related events allow agent access to fetus before birth or during parturition
Impaired innate and adaptive immune functions
Antibodies production and PMN (both in number, function) are poor in newborn, especially in prematurely born infants
nosocomial techniques and devices
Are often kept in 80% humidity, an environment where bacteria & fungi flourish.
Presence of multiple invasive devices:
Maternally related events allow agent access to fetus before birth or during parturition, such as
Premature rupture of membranes, esp. for greater than 24 hours.
Maternal infection during last week of pregnancy, e.g.,
Excessive manipulation during delivery
Use of intrauterine monitoring devices
Sources of etiologic agent:(neonate meningitis)
Infection acquired in utero (Common source):
From infected chorioamnionic and amniotic fluid.
From infected blood – via chord blood – transplacental transmission.
Infection during parturition, aspiration of infected vaginal secretions (Common source).
Infection acquired hours → days post-partum from caregiver(s).
Signs and symptoms of meningitis in the neonate are not the same as the adult and include:
GI disturbance (vomiting/diarrhea)/abdominal distension
Respiratory abnormalities (e.g., dyspnea, cyanosis)
Cardiac abnormalities (tachycardia)
neonatal meningitis px
generally poor, mortality rates vary from 10-60% with survivors showing some permanent defects (neurological sequelae) which may be significant
Streptococcus agalactiae - Group B Streptococci (GBS):
Gram-positive cocci in chains or pairs (AKA streptococci).
β-hemolytic on sheep blood agar via production of the ornithine rhamnolipid pigment or lipid toxin.
Bacitracin-resistant versus GAS, which is bacitracin- sensitive
S. agalactiae group based on ??
cell wall antigen
Lancefield's serological classification based primarily on cell wall carbohydrate (C carbohydrate, teichoic acids). Groups A→T. Groups A, B, D are clinically important.
S. agalactiae also serologically typed based on ??
Major virulence factor –
There are several (9) groups:
Five groups (especially Group III) are most common causes of both early and late onset disease.
S. agalactiae is the leading cause of ?? alone or with ?? within the first 3 months of life
meningitis and/or pneumonia as complications
Incidence is highest in pre-term, but most (75%) cases occur in full-term infants (more of those guys)
1/3 of all invasive GBS disease occurs in ??
pregnant women (Maternal UTI caused by GBS frequently occurs before or just after birth).
adults, esp. elderly can also get GBS
usually with chronic or immunosuppressive disease:
persons > 60 y-o-age is high (4 → 7 cases/100,000 population) with a high (25%) mortality rate.
Diabetes, cirrhosis, malignancy, AIDS.
*Clinical GBS syndromes occur in virtually all tissues/organs
GBS Transmission and Reservoir:
Vertical infection occurs before and/or during birth
Horizontal infection (mother/caregiver → newborn) occurs after birth.
Agent colonizes mother’s pharynx, vagina, and skin via rectal colonization:
-Not all gravid females are colonized by GBS.
-Not all gravid females colonized by GBS pass it to the neonate.
-Not all neonates carrying GBS become infected/diseased.
Two forms of neonatal disease are recognized:
Early (acute) onset sepsis (bacteremia)
Late (insidious) onset sepsis (bacteremia or focal infection)
Early (acute) onset sepsis (bacteremia):
Occurs within the first 6 days after birth.
Source is mother, infection is acquired in utero or via passage through birth canal.
More common form of disease (80% of cases)
Late (insidious) onset sepsis (bacteremia or focal infection):
Occurs 7 days → 3 months following birth.
Source: associated with postpartum acquisition in the nursery (care givers) or community or mothers.
Focal infections include:
Less common form of this disease (20% of cases)
Meningitis occurs in few (5%) cases of ?? but many (@30%) cases of ??
early onset sepsis
late onset sepsis
Because of the higher mortality rate and the occurrence of neurological sequelae associated with meningitis, have a high index of suspicion for meningitis
hemolytic GBS pigment triggers mast cell degranulation, resulting in the release of ??
mast cell degranulation in the lower genital tract can limit colonization of ??
preformed and proinflammatory mediators
hyperpigmented GBS strains
Isolation of GBS from:
the patient (i.e., neonate) from normally sterile sites:
Isolation of GBS from: the mom
Identification of the organism:
Rapid slide agglutination to ID GBS, based on C-specific substance/carbohydrate.
other tests - PCR
The screening approach for GBS:
all pregnant mothers be screened at 35→37 weeks gestation (Studies show that this is best approach)
2 specimens are collected, swabs from rectum and vagina
all identified carriers and women who deliver pre-term before screening should be offered intrapartum antimicrobial prophylaxis iv
intrapartum antimicrobial prophylaxis iv (GBS)
susceptibility to erythromycin and clindamycin has not been performed or has been found resistant
GBS: antibiotic prophylaxis before labor starts and single administration of postpartum antibiotic prophylaxis for newborns are ??
There are no reports of resistance to ?? but GBS resistance to ?? and ?? has been reported at 15-30% and 10-20% of cases, respectively
The risk factors assessment (non screening)approach for GBS
intrapartum antimicrobial agents (same antibiotics as stated above administered iv) should be offered to any pregnant women with 1 or more of the following risk factors:
elevated intrapartum temperature
membrane rupture > 18 hours
premature onset of labor
premature rupture of membrane (PROM) at
Many (NOT ALL) hospitals have adopted the CDC recommendations or give all mothers antibiotics and this has resulted in ??
a BIG decrease in GBS infections in neonates in US
There is no prevention strategy for ??
late onset GBS disease
Problems with Intrapartum Antibiotic Exposure:
with increased use of intrapartum antibiotics to reduce the incidence of neonatal GBS infection, the incidence of early onset sepsis in VLBW infants has not changed, but the ??? have changed
etiologic agents responsible
e.g., E. coli are now the primary etiologic agents
therapy is resulting in an increased incidence of late onset sepsis
A Gram positive, coccobacilli (rod), motile, coryneform species. (may look like cocci but are NOT)
Growth temperature range is broad (0→50o C). Isolated by cold enrichment, like Yersinia.
L. mono are IC or EC??
facultative intracellular pathogens
Invade & multiply in nonprofessional phagocytes: epithelial cells.
Survive and multiply within phagocytic cells such a:
non-activated macrophages and monocytes.
Listeria is Serologically heterogeneous
Numerous serotypes based on O & H antigens
*Three serotypes account for most infections in animals and humans
Virulence factors of listeria
Lipoteichoic acids (LPS-rare for G+): Immunomodulator as potent
Proteins: enzymes required for organism-directed phagocytosis and cell-to-cell spread.
sporadic cases and food-borne epidemics.
Listeria Transmission and reservoirs
Food-borne: ingestion is primary mode, esp. adults, rare disease but mortality is high.
in utero - transplacental (vertical) transfer.
during parturition (vertical) transmission.
Animal-to-human; a zoonosis.
Primary reservoirs: Listeria
distributed worldwide – is ubiquitous:
normal fecal flora of mammals - including humans: Human immune carriers exist.
Age and gender and seasonality of Listeria
SUMMER: food assoc.
Listeria risk factors
Immunosuppression - T cell suppression: These are the populations for which you should have a high index of suspicion of listeriosis!:
young/neonates (3rd leading cause of invasive neonatal disease).
Aged/elderly persons: >70 y-o-age (2/100,000),
Pregnant females (12/100,000),
Advanced HIV/AIDS pt: (70→210/100,000),
Other: Immunosuppressive therapy (esp. T cell deficiencies)
Incidnce of Listeria in the general population is ??
most cases due to ??
NOT common-source outbreaks
Organism is ingested → passes through the intestinal epithelium → bacteremia
Listeria POE is the ??
Agent is phagocytized by gastrointestinal cells (without damaging the integrity of the GI tract) and macrophages (agent survives in non-activated macrophages). Concurrent/Intercurrent GITI with another pathogen may promote infection with Listeria?
?? induce phagocytosis of Listeria by nonprofessional phagocytic cells (similar to Shigella) and also mediate entry into epithelial cell
Enzymes (esp. ??) disrupt the phagosome membrane allowing Listeria cells to escape from the host vacuole and replicate in the host cell cytoplasm
Cell-to-cell infection occurs when a tail of ?? form at the ends of the Listeria cells due to virulence factors, e.g., ??
Same mechanism is used by ??
polymerized actin filaments
Shigella sp., Rickettsia and vaccina virus
Listeria has a tropism for
CNS (meninges and brain, especially the brain-stem) and is capable of penetrating and infecting brain parenchyma (usually brain stem).
Listeria incubation period
may be long (about 30 days; range is 11→70 days).
Primarily T cell-mediated immunity
control of infection requires activated macrophages, which can only kill *stationary (latent*) phase Listeria*
(better pathogen than Mtb!)
Listeria Infections in pregnancy: occurrence and manifestations
Illness usually occurs in the 3rd trimester, with the greatest decline in gravid female’s CMI.
Gravid female manifests with acute, febrile illness - severe flu-like symptoms due to bacteremia. Mother rarely manifests with CNS infection
Outcomes of Listeria Fetal (in utero) infection:
early-onset sepsis syndrome,
spontaneous abortion (from 5m gestation on),
Fetal mortality rate is high (15→50%).
Listeria Early-onset sepsis syndrome:
is associated with prematurity.
Infection is likely acquired in utero via inhalation of infected amniotic fluid.
Agent is found in neonate practically everywhere (in the:
Symptoms manifest in newborn (
Listeria Granulomatosis infantisepticum is ??
agent found in ??
a rare condition involving in utero infection
disseminated abscess and/or granulomas in multiple internal organs, esp. liver & spleen.
papules in throat, skin may also be present.
Neonate mortality rate is high (>50%).
Listeria Late-onset meningoencephalitis
Infection occurs during or after birth.
Symptoms manifest in between 1→2 weeks postpartum.
Neonate mortality rate is moderate (10 → 20%).
Mother is asymptomatic.
Adults w/ Listeriosis manifest with one or more of:
Meningitis (acute or subacute)
Macroscopic brain abscess (mass lesions) with meningitis:
Seizures can occur
*Listeria has tropism for brain (esp. brain stem).
Bacteremia may → flu-like disease. Predisposing factors as stated above.
Focal non meningeal infections are uncommon
Listeria Food poisoning/gastroenteritis symptoms include:
occurs in who ??
arthropathy & myalgia
abdominal cramps, nausea, vomiting
Occurs in both immunocompetent and immunocompromised persons
Listeria ddx: based on
etiologic agents based on population
Listeria dx: Cx
blood (esp if pt. spikes or has a fever).
tissues including placenta.
feces (if present, present in low numbers [20 CFU/g feces]) so prolonged, cold-enrichment may improve chances of isolation.
detection in food (must be same serotype as that isolated from patient to prove source).
Listeria dx: Gram stain
Listeria dx: Gram stain limitations ??
morphology similar to either Corynebacterium sp. or coccobacilli.
easily decolorized (appear Gram-negative or not stained).
present in small numbers in feces, so easily missed
Listeria dx: CSF with listerial meningoencephalitis:
glucose level is often normal.
low probability of observing Listeria in CSF (
ampicillin + gentamycin. Alternative is TMP-SMX